From the HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Hematology and Bone Marrow Transplantation Unit, Cancer Immunotherapy and Gene Therapy Program, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Scientifico H. S. Raffaele, Milan, Italy; Immunogenetics Laboratory, Unit of Clinical Epidemiology and Trials, IRCCS National Institute for Cancer Research, Genoa, Italy; Department of Hematology, Imperial College, London, United Kingdom; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, Department of Pediatric Hematology-Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, Institute of Hematology and Medical Oncology, University of Bologna, Ospedale S. Orsola-Malpighi, Bologna, Italy; Department of Pediatric Hematology-Oncology, IRCCS G. Gaslini, Genoa, Italy; Department of Hematology, Ospedale San Martino, Genoa, Italy; and Department of Oncology, Biology and Genetics, University of Genoa, Genoa, Italy.
The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P = .046) and transplantation-related mortality (HR = 2.69, P = .027) but not relapse (HR = 0.98, P = .939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P = .1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation. (文章出处：《血液学杂志》)
The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P = .046) and transplantation-related mortality (HR = 2.69, P = .027) but not relapse (HR = 0.98, P = .939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P = .1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation. (文章出处：《血液学杂志》)